Propofol-induced deep sedation reduces emotional episodic memory reconsolidation in humans

Abstract

The adjustment of maladaptive thoughts and behaviors associated with emotional memories is central to treating psychiatric disorders. Recent research, predominantly with laboratory animals, indicates that memories can become temporarily sensitive to modification following reactivation, before undergoing reconsolidation. A method to selectively impair reconsolidation of specific emotional or traumatic memories in humans could translate to an effective treatment for conditions such as posttraumatic stress disorder. We tested whether deep sedation could impair emotional memory reconsolidation in 50 human participants. Administering the intravenous anesthetic propofol following memory reactivation disrupted memory for the reactivated, but not for a non-reactivated, slideshow story. Propofol impaired memory for the reactivated story after 24 hours, but not immediately after propofol recovery. Critically, memory impairment occurred selectively for the emotionally negative phase of the reactivated story. One dose of propofol following memory reactivation selectively impaired subsequent emotional episodic memory retrieval in a time-dependent manner, consistent with reconsolidation impairment.

Investigating the efficacy of the reminder-extinction procedure to disrupt contextual threat memories in humans using immersive Virtual Reality

“…We also did not find an effect of an isolated reminder before extinction on item-location spatial memory. These findings are in contrast to human and rodent studies which indicate that reconsolidation-based interventions can impair episodic 10,31,32,35,71,121 and spatial memories 122,123 . They are also in contrast to previous studies in rodents and humans that suggest that a reminder in the absence of reconsolidationinterventions, or when interventions fail, can strengthen aversive episodic and spatial memories 35,36,124 .…”

“…The limited replicability may not be limited the reminder-extinction procedure, but could generalize to reconsolidation-based interventions 106,107 . It would therefore be worthwhile to explore if other interventions such as beta-blockers 18,108 , propofol 33 , electrical brain stimulation 35 , or other behavioural interventions 109 are capable of permanently attenuating contextual threat memories in humans. By doing so, we will hopefully reach a more mechanistic understanding of how post-retrieval interventions can impact memories.…”

“…At present, it is unclear whether this could be because the reminder-extinction procedure is ineffective in modifying hippocampus-dependent contextual threat memories specifically, threat memories more generally, or because of alternative reasons. It would therefore be worthwhile to explore if other interventions such as beta-blockers 18,108 , propofol 33 , electrical brain stimulation 35 , or other behavioural interventions 109 are capable of permanently attenuating contextual threat memories in humans. Alternatively, even though we observed reactivation of contextual threat memory as indexed by threat-potentiated startle, our reminder procedure may simply have failed to reactivate memory in such a way that it resulted in destabilization of the memory.…”

“…Alternatively, even though we observed reactivation of contextual threat memory as indexed by threat-potentiated startle, our reminder procedure may simply have failed to reactivate memory in such a way that it resulted in destabilization of the memory. Many explanations and boundary conditions to the (non-)destabilization of memory can be proposed post-hoc, yet the exact conditions that allow the reactivation and destabilization of memories are rarely experimentally and prospectively investigated 121,131,132 , particularly in humans. We therefore strongly encourage future studies to investigate the mechanisms underlying the destabilization of memories.…”

“…a shock) in the absence of a discrete cue signalling the outcome 26 – 30 . In humans, however, supportive evidence for reconsolidation of hippocampus-dependent memories is more limited and in contrast to studies in rodents generally stems from outside the Pavlovian threat conditioning domain, relying on memory paradigms originating from the episodic memory domain, such as word-lists 31 , 32 or stories 10 , 33 – 35 . A recent study trying to unite approaches from the Pavlovian threat conditioning and episodic memory fields, using a category threat conditioning procedure in humans, indicated that episodic memory for items that were part of a Pavlovian threat conditioning experience can undergo reconsolidation, but that the efficacy of reconsolidation-interventions may decrease when episodic memory demands increase 36 , consistent with suggestions from studies with rodents 37 (see Ref.…”